Supplementary Material for: Benzodiazepines as a Monotherapy in Depressive Disorders: A Systematic Review

<b><i>Background:</i></b> The aim of this paper was to perform a systematic review and, when feasible, a meta-analysis of randomized controlled trials (RCT) which used benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD), or both. <b><i>Methods:</i></b> Keyword searches were conducted for identifying RCT comparing BZD and AD, and/or placebo in the treatment of depression, using electronic databases from their inception up to April 2017. We selected reports of RCT in which BZD were compared to AD and/or placebo in the treatment of adult patients with a primary diagnosis of depressive disorder or anxious depression. When feasible, data were subjected to meta-analysis. <b><i>Results:</i></b> A total of 38 studies met the criteria for inclusion and were then included in the systematic review. Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we submitted data on response rate from 22 RCT, considering BZD versus placebo (8 comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons). There was a lack of significant differences as to response rate between BZD and placebo, as well as between BZD and TCA. Analysis of individual studies disclosed that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD were significantly more effective than placebo and as effective as TCA. <b><i>Conclusions:</i></b> BZD are a therapeutic option in anxious depression and there are no indications that AD are preferable. There is a pressing need for RCT of adequate methodological quality and follow-up comparing BZD to second-generation AD and placebo in anxious depression.

**背景：** 本研究旨在开展一项系统综述，并在可行的情况下，针对以苯二氮䓬类药物（BZD）单药治疗对比安慰剂、抗抑郁药物（AD），或二者联合的随机对照试验（RCT）进行荟萃分析。
**方法：** 本研究通过自建库起至2017年4月的电子数据库，以关键词检索识别对比BZD与AD和/或安慰剂治疗抑郁症的随机对照试验（RCT）。我们筛选了针对确诊为抑郁障碍或焦虑性抑郁的成年患者，将BZD与AD和/或安慰剂对比的RCT研究报告。若条件允许，将对数据开展荟萃分析。
**结果：** 共计38项研究符合纳入标准，被纳入本次系统综述。其中仅有1项研究涉及新型抗抑郁药物氟伏沙明（fluvoxamine）。针对荟萃分析，我们纳入了22项RCT的应答率数据，涵盖BZD对比安慰剂（8组对照）以及BZD对比三环类抗抑郁药（TCA，20组对照）的研究。结果显示，BZD与安慰剂之间、BZD与TCA之间的应答率均无显著差异。对单项研究的分析表明，在超过半数对比BZD与TCA和/或安慰剂的研究中，BZD的疗效显著优于安慰剂，且与TCA相当。
**结论：** BZD可作为焦虑性抑郁的治疗选择，尚无证据表明AD更具优势。目前亟需开展方法学质量合格且具备随访的随机对照试验，对比BZD与第二代抗抑郁药物（second-generation AD）及安慰剂治疗焦虑性抑郁的效果。